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The Effector Domain of Human Dlg Tumor Suppressor Acts as a Switch That Relieves Autoinhibition of Kinesin-3 Motor GAKIN/KIF13B †
journal contributionposted on 2023-02-23, 18:23 authored by Kaori YamadaKaori Yamada, Toshihiko Hanada, Athar H Chishti
The activity of motor proteins must be tightly regulated in the cells to prevent unnecessary energy consumption and to maintain proper distribution of cellular components. Loading of the cargo molecule is one likely mechanism to activate an inactive motor. Here, we report that the activity of the kinesin-3 motor protein, GAKIN, is regulated by the direct binding of its protein cargo, human discs large (hDlg) tumor suppressor. Recombinant GAKIN exhibits potent microtubule gliding activity but has little microtubule-stimulated ATPase activity in solution, suggesting that it exists in an autoinhibitory form. In vitro binding measurements revealed that defined segments of GAKIN, particularly the MAGUK binding stalk (MBS) domain and the motor domain, mediate intramolecular interactions to confer globular protein conformation. Direct binding of the SH3-I3-GUK module of hDlg to the MBS domain of GAKIN activates the microtubule-stimulated ATPase activity of GAKIN by approximately 10-fold. We propose that the cargo-mediated regulation of motor activity constitutes a general paradigm for the activation of kinesins.
Cytoskeletal Interaction of Human Dlg Protein | Funder: National Institutes of Health (National Cancer Institute) | Grant ID: R01CA094414
CitationYamada, K. H., Hanada, T.Chishti, A. H. (2007). The Effector Domain of Human Dlg Tumor Suppressor Acts as a Switch That Relieves Autoinhibition of Kinesin-3 Motor GAKIN/KIF13B †. Biochemistry, 46(35), 10039-10045. https://doi.org/10.1021/bi701169w
PublisherAmerican Chemical Society (ACS)
CategoriesNo categories selected
1.1 Normal biological development and functioningCancerGeneric health relevanceAdaptor Proteins, Signal TransducingAdenosine TriphosphatasesAnimalsCarrier ProteinsDiscs Large Homolog 1 ProteinEnzyme ReactivatorsHumansKinesinsMembrane ProteinsMicrotubule-Associated ProteinsModels, BiologicalModels, MolecularMolecular Motor ProteinsMolecular Sequence DataProtein BindingProtein Structure, TertiaryProtein TransportRecombinant Fusion ProteinsBiochemistry & Molecular BiologyMedicinal and Biomolecular ChemistryBiochemistry and Cell BiologyMedical Biochemistry and Metabolomics